The field of the invention is inhibition of virus replication.
Viruses are simple forms of replicating obligate intracellular parasites that are important animal (including human) pathogens. Viruses are classified into families according to their structure and genetic composition and thus comprise two major groups, DNA and RNA viruses. DNA virus families include the Poxviruses, Herpesviruses, Adenoviruses, Papovaviruses, Parvoviruses and Hepadnaviruses.
Herpes simplex virus type 1 (HSV-1) is a member of the herpesvirus family. A ubiquitous property of the herpesviruses is their capacity to remain latent in the host in which they multiply.
HSV-1 contains a linear double-stranded DNA genome 152 kilobases in length which encodes more than 72 gene products (McGeoch et al., 1988, J. Gen. Virol. 69:1531). The products of seven viral genes are required for origin-dependent replication of the viral genome (McGneoch et al., 1988, J. Virol. 62:444; Olivo et al., 1989, J. Virol. 63:196; Wu et al., 1988, J. Virol. 62:435). These seven viral genes include the origin binding protein (OBP), the single-stranded DNA binding protein (ICP8), the viral DNA polymerase, the polymerase accessory protein, and three proteins comprising a helicase-primase complex (Challberg et al., 1989, Ann. Rev. Biochem. 58:671). Although necessary, these proteins are not sufficient for origin-dependent DNA synthesis outside the cellular milieu.
The HSV-1 genome contains two covalently linked segments termed the unique long (U.sub.L) and unique short (U.sub.S) segments. Each segment is flanked by inverted repeat sequences, the internal (IR) and terminal (TR) repeats. The genome contains three origins of DNA replication, one located within U.sub.L (oriL) and two within the repeat sequences flanking U.sub.S (oriS) (Challberg et al., 1989, Ann. Rev. Biochem. 58:671; Spaete et al., 1985, Proc. Natl. Acad. Sci. USA 82:694; Stow et al., Virology 130:427).